This is a resubmission of I K07 CA096619-01 "Diet, Hormone Replacement Therapy and Breast Cancer". Candidate: Shumin Zhang received her MD at the Harbin Medical University in 1986 and her ScD in epidemiology and nutrition at the Harvard School of Public Health in 1998. She then completed her post-doctoral training in 2000, and now is an Assistant Professor of Medicine at the Harvard Medical School (HMS). She applies for this Career Development Award to acquire the methodological and theoretical research skills needed to become an independent scientist in cancer and nutritional epidemiology. Sponsor and Environment: JoAnn Manson, MD, DrPH, is the Chief of the Division of Preventive Medicine at the Brigham and Women's Hospital, Professor of Medicine at the HMS and Co Principal investigator (Co-Principal Investigator) of the Women's Health Study ONHS). Julie Buring, ScD, is the Deputy Director of the Division, Professor of Ambulatory Care and Prevention at the HMS and Principal Investigator of the WHS. They have trained numerous investigators in the fields of diet, lifestyle and chronic diseases, areas in which they have published extensively. Research: We plan to conduct a prospective analysis within the WHS, an ongoing clinical trial of vitamin E and low-dose aspirin in the primary prevention of cancer and cardiovascular disease among 39,876 women. We will test 4 dietary hypotheses that moderate alcohol intake increases risk of breast cancer, whereas high intake of folate and fiber reduces risk; and caffeine intake is not associated with risk. We will link fiber intake to plasma endogenous sex steroid hormones in a subsample of the WHS. We will also test 4 hormone replacement therapy (HRT) hypotheses that tong-term use of estrogen plus progestin increases risk of breast cancer more than estrogen alone; estrogen plus cyclic progestin increases risk more than estrogen plus continuous progestin; low-dose estrogens confer lower risk than high-dose; and use of estrogen is more strongly associated with risk among women drinking alcohol. The ongoing WHS will provide updated and repeated measures of HRT, comprehensive dietary assessment at baseline, and important covariates for breast cancer in addition to follow-up of the cohort and documentation of breast cancer cases (expected N = 1550). The findings from this project could have direct clinical application for efforts to reduce risk of breast cancer.